Polymer Matrix-Based Carbon Nanocomposites for Neural Tissue Engineering

Springer Science and Business Media LLC - Tập 7 - Trang 93-114 - 2021
Souvik Ghosh1,2,3, Partha Roy2, Debrupa Lahiri1,2
1Biomaterials and Multiscale Mechanics Lab, Department of Metallurgical and Materials Engineering, Indian Institute of Technology Roorkee, Roorkee, India
2Molecular Endocrinology Lab, Department of Biosciences and Bioengineering, Indian Institute of Technology Roorkee, Roorkee, India
3Centre of Nanotechnology, Indian Institute of Technology Roorkee, Roorkee, India

Tóm tắt

Nanomaterials have been extensively used to develop potent regenerative medicine against diseased and damaged nervous tissues concerning memory, cognition, and locomotion. The exquisite properties such as mechanical, thermal, and electrical properties of carbon-based nanomaterials (graphene and carbon nanotubes) render them the ability to drive neural tissue repair and regeneration. This review mainly focuses on the importance of carbon nanomaterials and their polymeric composites in nerve tissue engineering applications. Along with that, we also discuss about the properties of the scaffolds, types of materials used, different types of composite preparation methods, and background of synthesis of polymer nanocomposites for neural tissue engineering. Moreover, current limitations of using carbon nanomaterials in tissue engineering are also explored along with the future prospective. Overall, this article reviews carbon nanomaterial-based polymer composites as promising “next-generation” treatment strategies in the area of neural tissue engineering.

Tài liệu tham khảo

Ahn HS, Hwang JY, Kim MS, Lee JY, Kim JW, Kim HS, Hyun JK (2015) Carbon-nanotube-interfaced glass fiber scaffold for regeneration of transected sciatic nerve. Acta Biomater 13:324–334. https://doi.org/10.1016/j.actbio.2014.11.026 Ai J, Kiasat-dolatabadi A, Ebrahimi-barough S, Ai A, Norouzi-javidan A, Saberi H, Aghayan R (2014) Polymeric Scaffolds in neural tissue engineering: a review. Arch Neurosci 1(1):15–20. https://doi.org/10.5812/archneurosci.9144 Akhavan O, Ghaderi E, Abouei E, Hatamie S, Ghasemi E (2014) Accelerated differentiation of neural stem cells into neurons on ginseng-reduced graphene oxide sheets. Carbon 66:395–406. https://doi.org/10.1016/j.carbon.2013.09.015 Al Sheheri SZ, Al-Amshany ZM, Al Sulami QA, Tashkandi NY, Hussein MA, El-Shishtawy RM (2019) The preparation of carbon nanofillers and their role on the performance of variable polymer nanocomposites. Des Monomers Polym 22(1):8–53. https://doi.org/10.1080/15685551.2019.1565664 Anandhan S, Bandyopadhyay S (2011) Polymer nanocomposites: from synthesis to applications. In: Nanocomposites and polymers with analytical methods, pp 1–28. https://doi.org/10.5772/17039 Arslantunali D, Budak G, Hasirci V (2014) Multiwalled CNT-pHEMA composite conduit for peripheral nerve repair. J Biomed Mater Res Part A 102(3):828–841. https://doi.org/10.1002/jbm.a.34727 Bacon R (1960) Growth, structure, and properties of graphite whiskers. J Appl Phys 31(2):283–290. https://doi.org/10.1021/cen-v035n023.p032 Balandin AA, Ghosh S, Bao W, Calizo I, Teweldebrhan D, Miao F, Lau CN (2008) Superior thermal conductivity of single-layer graphene. Nano Lett 8(3):902–907. https://doi.org/10.1021/nl0731872 Bei HP, Yang Y, Zhang Q, Tian Y, Luo X, Yang M, Zhao X (2019) Graphene-based nanocomposites for neural tissue engineering. Molecules 24(658):1–15. https://doi.org/10.3390/molecules24040658 Bhuyan MSA, Uddin MN, Islam MM, Bipasha FA, Hossain SS (2016) Synthesis of graphene. Int Nano Lett 6(2):65–83. https://doi.org/10.1007/s40089-015-0176-1 Boni R, Ali A, Shavandi A, Clarkson AN (2018) Current and novel polymeric biomaterials for neural tissue engineering. J Biomed Sci 25(1):1–21. https://doi.org/10.1186/s12929-018-0491-8 Bosi S, Fabbro A, Ballerini L, Prato M (2013) Carbon nanotubes: a promise for nerve tissue engineering ? Nanotechnol Rev 2(1):47–57. https://doi.org/10.1515/ntrev-2012-0067 Bramini M, Alberini G, Colombo E, Chiacchiaretta M, DiFrancesco ML, Maya-Vetencourt JF, Cesca F (2018) Interfacing graphene-based materials with neural cells. Front Syst Neurosci 12(12):1–22. https://doi.org/10.3389/fnsys.2018.00012 Butler SJ, Bronner ME (2016) From classical to current: analyzing peripheral nervous system and spinal cord lineage and fate. Dev Biol 398(2):135–146. https://doi.org/10.1016/j.ydbio.2014.09.033.From Coopera CA, Ravicha D, Lipsb D, Joerg Mayerb HDW (2002) Distribution and alignment of carbon nanotubes and nanofibrils.PDF. Compos Sci Technol 62:1105–1112 Cassell AM, Raymakers JA, Kong J, Dai H (1999) Large scale CVD synthesis of single-walled carbon nanotubes. J Phys Chem B 103(31):6484–6492. https://doi.org/10.1021/jp990957s Chang KA, Kim JW, Kim JA, Lee S, Kim S, Suh WH, Suh YH (2011) Biphasic electrical currents stimulation promotes both proliferation and differentiation of fetal neural stem cells. PLoS ONE 6(4):e18738. https://doi.org/10.1371/journal.pone.0018738 Chen J, Chu B, Hsiao BS (2006) Mineralization of hydroxyapatite in electrospun nanofibrous poly(L-lactic acid) scaffolds. InterScience 79(2):307–317. https://doi.org/10.1002/jbm.a Chiara GD (1997) The principles of nerve cell communication. Alcohol Health Res World 21(2):107–108 Cho Y, Borgens RB (2010) The effect of an electrically conductive carbon nanotube/collagen composite on neurite outgrowth of PC12 cells. J Biomed Mater Res Part A 95A(2):510–517. https://doi.org/10.1002/jbm.a.32841 Chowdhury I, Mansukhani ND, Guiney LM, Hersam MC, Bouchard D (2015) Aggregation and stability of reduced graphene oxide: complex roles of divalent cations, pH, and natural organic matter. Environ Sci Technol 49(18):10886–10893. https://doi.org/10.1021/acs.est.5b01866 Colognato H, Tzvetanova ID (2011) Glia unglued: How signals from the extracellular matrix regulate the development of myelinating glia. Dev Neurobiol 71(11):924–955. https://doi.org/10.1002/dneu.20966 Dundigalla A, Lin-Gibson S, Ferreiro V, Malwitz MM, Schmidt G (2005) Unusual multilayered structures in poly(ethylene oxide)/laponite nanocomposite films. Macromol Rapid Commun 26(3):143–149. https://doi.org/10.1002/marc.200400489 Esrafilzadeh D, Jalili R, Stewart EM, Aboutalebi SH, Razal JM, Moulton SE, Wallace GG (2016) High-performance multifunctional graphene-plga fibers: toward biomimetic and conducting 3D Scaffolds. Adv Func Mater 26(18):3105–3117. https://doi.org/10.1002/adfm.201505304 Feng Z, Wang T, Zhao B, Li J, Jin L (2015) Soft graphene nanofi bers designed for the acceleration of nerve growth and development. Adv Mater 27:6462–6468. https://doi.org/10.1002/adma.201503319 Fields RD (2012) Glial cells. In: Encyclopedia of human behavior: second edition. Elsevier Inc, pp. 255–260. https://doi.org/10.1016/B978-0-12-375000-6.00181-6 Fitch MT, Silver J (2008) CNS injury, glial scars, and inflammation: inhibitory extracellular matrices and regeneration failure. Exp Neurol 209(2):294–301 Fu C, Pan S, Ma Y, Kong W, Qi Z, Yang X (2019a) Effect of electrical stimulation combined with graphene-oxide-based membranes on neural stem cell proliferation and differentiation. Artif Cells Nanomed Biotechnol 47(1):1867–1876. https://doi.org/10.1080/21691401.2019.1613422 Fu S, Sun Z, Huang P, Li Y, Hu N (2019b) Some basic aspects of polymer nanocomposites: a critical review. Nano Mater Sci 1(1):2–30. https://doi.org/10.1016/j.nanoms.2019.02.006 Furth ME, Atala A (2013) Tissue engineering: future perspectives. In: Principles of tissue engineering: fourth edition. Elsevier, pp 83–123. https://doi.org/10.1016/B978-0-12-398358-9.00006-9 Fusco S, Panzetta V, Embrione V, Netti PA (2015) Crosstalk between focal adhesions and material mechanical properties governs cell mechanics and functions. Acta Biomater 23:63–71. https://doi.org/10.1016/j.actbio.2015.05.008 Gaharwar AK, Dammu SA, Canter JM, Wu CJ, Schmidt G (2011) Highly extensible, tough, and elastomeric nanocomposite hydrogels from poly(ethylene glycol) and hydroxyapatite nanoparticles. Biomacromol 12(5):1641–1650. https://doi.org/10.1021/bm200027z Galvan-Garcia P, Keefer EW, Yang F, Zhang M, Fang S, Zakhidov AA, Romero MI (2007) Robust cell migration and neuronal growth on pristine carbon nanotube sheets and yarns. J Biomater Sci Polym Ed 18(10):1245–1261. https://doi.org/10.1163/156856207782177891 Ghosh S, Haldar S, Gupta S, Bisht A, Chauhan S, Kumar V, Lahiri D (2020) Anisotropically conductive biodegradable Scaffold with coaxially aligned carbon nanotubes for directional regeneration of peripheral nerves. ACS Appl Bio Mater 3:5796–5812. https://doi.org/10.1021/acsabm.0c00534 Ghosh S, Shrivastava A, Jha P, Roy P, Lahiri D (2021) Analysis of neural cell behaviour on anisotropic electrically conductive polymeric biodegradable scaffolds reinforced with carbon nanotubes. Med Devices Sens 4(1):1–15 Goenka S, Sant V, Sant S (2014) Graphene-based nanomaterials for drug delivery and tissue engineering. J Control Release 173(1):75–88. https://doi.org/10.1016/j.jconrel.2013.10.017 Gupta P, Sharan S, Roy P, Lahiri D (2015) Aligned carbon nanotube reinforced polymeric scaffolds with electrical cues for neural tissue regeneration. Carbon 95:715–724. https://doi.org/10.1016/j.carbon.2015.08.107 Gupta P, Agrawal A, Murali K, Varshney R, Beniwal S, Manhas S, Lahiri D (2019) Differential neural cell adhesion and neurite outgrowth on carbon nanotube and graphene reinforced polymeric scaffolds. Mater Sci Eng, C 97:539–551. https://doi.org/10.1016/j.msec.2018.12.065 He J, Wang XM, Spector M, Cui FZ (2012) Scaffolds for central nervous system tissue engineering. Front Mater Sci 6(1):1–25. https://doi.org/10.1007/s11706-012-0157-5 Hopley EL, Salmasi S, Kalaskar DM, Seifalian AM (2014) Carbon nanotubes leading the way forward in new generation 3D tissue engineering. Biotechnol Adv 32(5):1000–1014. https://doi.org/10.1016/j.biotechadv.2014.05.003 Hu H, Ni Y, Montana V, Haddon RC, Parpura V (2004) Chemically functionalized carbon nanotubes as substrates for neuronal growth. Nano Lett 4(3):507–511. https://doi.org/10.1021/nl035193d Hu W, Peng C, Lv M, Li X, Zhang Y, Chen N, Huang Q (2011) Protein corona-mediated mitigation of cytotoxicity of graphene oxide. ACS Nano 5(5):3693–3700. https://doi.org/10.1021/nn200021j Huang YC, Hsu SH, Kuo WC, Chang-Chien CL, Cheng H, Huang YY (2011) Effects of laminin-coated carbon nanotube/chitosan fibers on guided neurite growth. J Biomed Mater Res Part A 99A(1):86–93. https://doi.org/10.1002/jbm.a.33164 Huang B, Vyas C, Roberts I, Poutrel QA, Chiang WH, Blaker JJ, Bártolo P (2019) Fabrication and characterisation of 3D printed MWCNT composite porous scaffolds for bone regeneration. Mater Sci Eng, C 98:266–278. https://doi.org/10.1016/j.msec.2018.12.100 Huebner EA, Strittmatter SM (2009) Axon regeneration in the peripheral and central nervous systems. Results Probl Cell Differ 48:339–351. https://doi.org/10.1007/400 Jan E, Kotov NA (2007) Successful differentiation of mouse neural stem cells on layer-by-layer assembled single-walled carbon nanotube composite. Nano Lett 7(5):1123–1128. https://doi.org/10.1021/nl0620132 Journet C, Maser WK, Bernier P, Loiseau A, Lamy de la Chapelle M, Lefrant S, Fischer JE (1997) Large-scale production of single-walled carbon nanotubes by the electric-arc technique. Nature 388:756–758. https://doi.org/10.1038/41972 Jung YL, Donahue HJ (2007) Cell sensing and response to micro- and nanostructured surfaces produced by chemical and topographic patterning. Tissue Eng 13(8):1879–1891. https://doi.org/10.1089/ten.2006.0154 Karak N (2019) Fundamentals of Nanomaterials and Polymer Nanocomposites. In: Nanomaterials and polymer nanocomposites, pp 1–45. Elsevier Inc. https://doi.org/10.1016/B978-0-12-814615-6.00001-1 Kickelbick G (2007) Introduction to hybrid materials. In: Hybrid materials: synthesis, characterization, and applications, pp 1–48. https://doi.org/10.1002/9783527610495.ch1 Kim DH, Martin DC (2006) Sustained release of dexamethasone from hydrophilic matrices using PLGA nanoparticles for neural drug delivery. Biomaterials 27(15):3031–3037. https://doi.org/10.1016/j.biomaterials.2005.12.021 Kim DH, Abidian M, Martin DC (2004) Conducting polymers grown in hydrogel scaffolds coated on neural prosthetic devices. J Biomed Mater Res Part A 71(4):577–585. https://doi.org/10.1002/jbm.a.30124 Kim MS, Yu JM, Kim HJ, Kim HB, Kim ST, Jang SK, Joo SS (2014) Ginsenoside Re and Rd enhance the expression of cholinergic markers and neuronal differentiation in neuro-2a cells. Biol Pharm Bull 37(5):826–833. https://doi.org/10.1248/bpb.b14-00011 Knott G, Molnar Z (2001) Cells of the nervous system. in: Encyclopedia of life sciences, pp 1–8. https://doi.org/10.1038/npg.els.0000031 Konwarh R, Karak N, Misra M (2013) Electrospun cellulose acetate nanofibers: the present status and gamut of biotechnological applications. Biotechnol Adv 31(4):421–437. https://doi.org/10.1016/j.biotechadv.2013.01.002 Koppes AN, Keating KW, McGregor AL, Koppes RA, Kearns KR, Ziemba AM, Thompson DM (2016) Robust neurite extension following exogenous electrical stimulation within single walled carbon nanotube-composite hydrogels. Acta Biomater 39:34–43. https://doi.org/10.1016/j.actbio.2016.05.014 Ku SH, Lee M, Park CB (2013) Carbon-based nanomaterials for tissue engineering. Adv Healthc Mater 2(2):244–260. https://doi.org/10.1002/adhm.201200307 Kumar AP, Depan D, Singh Tomer N, Singh RP (2009) Nanoscale particles for polymer degradation and stabilization—trends and future perspectives. Progress Polym Sci (oxford) 34(6):479–515. https://doi.org/10.1016/j.progpolymsci.2009.01.002 Kuzum D, Takano H, Shim E, Reed JC, Juul H, Richardson AG, Litt B (2014) Transparent and flexible low noise graphene electrodes for simultaneous electrophysiology and neuroimaging. Nat Commun 5:1–10. https://doi.org/10.1038/ncomms6259 Lee S, Spencer ND (2008) Sweet, hairy, soft, and slippery. Science 319:575–576 Lee WC, Lim CHYX, Shi H, Tang LAL, Wang Y, Lim CT, Loh KP (2011) Origin of enhanced stem cell growth and differentiation on graphene and graphene oxide. ACS Nano 5(9):7334–7341. https://doi.org/10.1021/nn202190c Lee SJ, Zhu W, Nowicki M, Lee G, Heo DN, Kim J, Zhang LG (2019) 3D printing nano conductive multi-walled carbon nanotube scaffolds for nerve regeneration. Mater Res Express 15(1):016018 Lewitus DY, Landers J, Branch JR, Smith KL, Callegari G, Kohn J, Neimark AV (2011) Biohybrid carbon nanotube/agarose fibers for neural tissue engineering. Adv Funct Mater 21(14):2624–2632. https://doi.org/10.1002/adfm.201002429 Liff SM, Kumar N, McKinley GH (2007) High-performance elastomeric nanocomposites via solvent-exchange processing. Nat Mater 6(1):76–83. https://doi.org/10.1038/nmat1798 Lin K, Yang D, Chu I, Cheng F, Chen C, Ho S, Pan H (2010) DuraSeal as a ligature in the anastomosis of rat sciatic nerve gap injury. J Surg Res 161(1):101–110. https://doi.org/10.1016/j.jss.2008.10.020 Liu Z, Dong X, Song L, Zhang H, Liu L, Zhu D, Leng X (2014) Carboxylation of multiwalled carbon nanotube enhanced its biocompatibility with L02 cells through decreased activation of mitochondrial apoptotic pathway. J Biomed Mater Res Part A 102(3):665–673. https://doi.org/10.1002/jbm.a.34729 Liu X, Miller AL, Park S, Waletzki BE, Terzic A, Yaszemski MJ, Lu L (2016) Covalent crosslinking of graphene oxide and carbon nanotube into hydrogels enhances nerve cell responses. J Mater Chem B 4(43):6930–6941. https://doi.org/10.1039/c6tb01722c lijima S (1991) Helical microtubules of graphitic carbon. Nature 354:56–58 Lloyd-Evans E, Waller-Evans H (2020) Biosynthesis and signalling functions of central and peripheral nervous system neurosteroids in health and disease. Essays Biochem 64(3):591–606. https://doi.org/10.1042/EBC20200043 Lu J, Cheng C, He YS, Lyu C, Wang Y, Yu J, Li D (2016) Multilayered graphene hydrogel membranes for guided bone regeneration. Adv Mater 28(21):4025–4031. https://doi.org/10.1002/adma.201505375 Lv ZJ, Liu Y, Miao H, Leng ZQ, Guo JH, Liu J (2017) Effects of multiwalled carbon nanotubes on electrospun poly(lactide-co-glycolide)-based nanocomposite scaffolds on neural cells proliferation. J Biomed Mater Res Part B Appl Biomater 105(5):934–943. https://doi.org/10.1002/jbm.b.33620 Ma Q, Yang L, Jiang Z, Song Q, Xiao M, Zhang D, Cheng G (2016) Three-dimensional stiff graphene scaffold on neural stem cells behavior. ACS Appl Mater Interfaces 8(50):34227–34233. https://doi.org/10.1021/acsami.6b12305 MacOssay J, Ybarra AVR, Arjamend FA, Cantu T, Eubanks TM, Chipara M, Mohamed-Noriega N (2012) Electrospun polystyrene-multiwalled carbon nanotubes: imaging, thermal and spectroscopic characterization. Des Monomers Polym 15(2):197–205. https://doi.org/10.1163/156855511X615065 Mahmoudifard M, Soleimani M, Hatamie S, Zamanlui S, Ranjbarvan P, Vossoughi M, Hosseinzadeh S (2016) The different fate of satellite cells on conductive composite electrospun nanofibers with graphene and graphene oxide nanosheets. Biomed Mater (bristol). https://doi.org/10.1088/1748-6041/11/2/025006 Matai I, Kaur G, Seyedsalehi A, McClinton A, Laurencin CT (2020) Progress in 3D bioprinting technology for tissue/organ regenerative engineering. Biomaterials 226:119536. https://doi.org/10.1016/j.biomaterials.2019.119536 Mayorga AG, Dolado EL, Gutierrez MC, Collazos-Castro JE, Luisa Ferrer M, Del Monte F, Serrano MC (2017) Favorable biological responses of neural cells and tissue interacting with graphene oxide microfibers. ACS Omega 2(11):8253–8263. https://doi.org/10.1021/acsomega.7b01354 McNally T, Murphy WR, Lew CY, Turner RJ, Brennan GP (2003) Polyamide-12 layered silicate nanocomposites by melt blending. Polymer 44(9):2761–2772. https://doi.org/10.1016/S0032-3861(03)00170-8 Mitragotri S, Lahann J (2009) Physical approaches to biomaterial design. Nat Mater 8(1):15–23. https://doi.org/10.1038/nmat2344 Mittal V (2009) Polymer layered silicate nanocomposites: a review. Materials 2:992–1057. https://doi.org/10.3390/ma2030992 Muller J, Huaux F, Fonseca A, Nagy JB, Moreau N, Delos M, Lison D (2008) Structural defects play a major role in the acute lung toxicity of multiwall carbon nanotubes: physicochemical aspects. Chem Res Toxicol 21(9):1690–1697. https://doi.org/10.1021/tx800100s Murphy FA, Poland CA, Duffin R, Donaldson K (2013) Length-dependent pleural inflammation and parietal pleural responses after deposition of carbon nanotubes in the pulmonary airspaces of mice. Nanotoxicology 7(6):1157–1167. https://doi.org/10.3109/17435390.2012.713527 Nieto A, Dua R, Zhang C, Boesl B, Ramaswamy S, Agarwal A (2015) Three dimensional graphene foam/polymer hybrid as a high strength biocompatible scaffold. Adv Funct Mater 25(25):3916–3924. https://doi.org/10.1002/adfm.201500876 Nisbet DR, Yu LMY, Zahir T, Forsythe JS (2012) Characterization of neural stem cells on electrospun poly (ε -caprolactone) submicron scaffolds: evaluating their potential in neural tissue engineering. J Biomater Sci Polym Ed 19(5):623–634 Novoselov KS, Geim AK, Morozov SV, Jiang D, Zhang Y, Dubonos SV, Firsov AA (2016) Electric field effect in atomically thin carbon films. Science 306:666–669 O’Brien FJ (2011) Biomaterials & scaffolds for tissue engineering. Mater Today 14(3):88–95. https://doi.org/10.1016/S1369-7021(11)70058-X Park DW, Schendel AA, Mikael S, Brodnick SK, Richner TJ, Ness JP, Williams JC (2014) Graphene-based carbon-layered electrode array technology for neural imaging and optogenetic applications. Nat Commun 5:1–11. https://doi.org/10.1038/ncomms6258 Paul DR, Robeson LM (2008) Polymer nanotechnology: nanocomposites. Polymer 49(15):3187–3204. https://doi.org/10.1016/j.polymer.2008.04.017 Pavlidou S, Papaspyrides CD (2008) A review on polymer-layered silicate nanocomposites. Prog Polym Sci 33(12):1119–1198. https://doi.org/10.1016/j.progpolymsci.2008.07.008 Pop E, Varshney V, Roy AK (2012) Thermal properties of graphene: fundamentals and applications. MRS Bull 37:1273 Qian Y, Zhao X, Han Q, Chen W, Li H, Yuan W (2018) An integrated multi-layer 3D-fabrication of PDA/RGD coated graphene loaded PCL nanoscaffold for peripheral nerve restoration. Nat Commun. https://doi.org/10.1038/s41467-017-02598-7 Redondo-Gómez C, Leandro-Mora R, Blanch-Bermúdez D, Espinoza-Araya C, Hidalgo-Barrantes D, Vega-Baudrit J (2020) Recent advances in carbon nanotubes for nervous tissue regeneration. Adv Polym Technol 2020:1–16. https://doi.org/10.1155/2020/6861205 Salehi M, Naseri-Nosar M, Ebrahimi-Barough S, Nourani M, Khojasteh A, Hamidieh AA, Ai J (2018) Sciatic nerve regeneration by transplantation of Schwann cells via erythropoietin controlled-releasing polylactic acid/multiwalled carbon nanotubes/gelatin nanofibrils neural guidance conduit. J Biomed Mater Res Part B Appl Biomater 106(4):1463–1476. https://doi.org/10.1002/jbm.b.33952 Sang M, Shin J, Kim K, Yu KJ (2019) Electronic and thermal properties of graphene and recent advances in graphene based electronics applications. Nanomaterials 9(3):1–33. https://doi.org/10.3390/nano9030374 Satarkar NS, Biswal D, Hilt JZ (2010) Hydrogel nanocomposites: a review of applications as remote controlled biomaterials. Soft Matter 6(11):2364–2371. https://doi.org/10.1039/b925218p Serrano MC, Gutiérrez MC, Del Monte F (2014) Role of polymers in the design of 3D carbon nanotube-based scaffolds for biomedical applications. Prog Polym Sci 39(7):1448–1471. https://doi.org/10.1016/j.progpolymsci.2014.02.004 Severino FPU, Ban J, Song Q, Tang M, Bianconi G, Cheng G, Torre V (2016) The role of dimensionality in neuronal network dynamics. Sci Rep 6:1–14. https://doi.org/10.1038/srep29640 Shah S, Yin PT, Uehara TM, Chueng STD, Yang L, Lee KB (2014) Guiding stem cell differentiation into oligodendrocytes using graphene-nanofiber hybrid scaffolds. Adv Mater 26(22):3673–3680. https://doi.org/10.1002/adma.201400523 Shao H, Li T, Zhu R, Xu X, Yu J, Chen S, He L (2018) Carbon nanotube multilayered nanocomposites as multifunctional substrates for actuating neuronal differentiation and functions of neural stem cells. Biomaterials 175:93–109. https://doi.org/10.1016/j.biomaterials.2018.05.028 Shastri VP (2006) Future of regenerative medicine: challenges and hurdles. Artif Organs 30(10):828–834. https://doi.org/10.1111/j.1525-1594.2006.00307.x Shokrgozar MA, Mottaghitalab F, Mottaghitalab V, Farokhi M (2011) Fabrication of porous chitosan/poly(vinyl alcohol) reinforced single-walled carbon nanotube nanocomposites for neural tissue engineering. J Biomed Nanotechnol 7:276–284. https://doi.org/10.1166/jbn.2011.1284 Shrestha S, Shrestha BK, Kim JI, Won Ko S, Park CH, Kim CS (2018) Electrodeless coating polypyrrole on chitosan grafted polyurethane with functionalized multiwall carbon nanotubes electrospun scaffold for nerve tissue engineering. Carbon 136:430–443. https://doi.org/10.1016/j.carbon.2018.04.064 Sladjana UZ, Ivan JD, Bratislav SD (2008) Microanatomical structure of the human sciatic nerve. Surg Radiol Anat 30(8):619–626. https://doi.org/10.1007/s00276-008-0386-6 Solanki A, Chueng STD, Yin PT, Kappera R, Chhowalla M, Lee KB (2013) Axonal alignment and enhanced neuronal differentiation of neural stem cells on graphene-nanoparticle hybrid structures. Adv Mater 25(38):5477–5482. https://doi.org/10.1002/adma.201302219 Soleimani M, Mashayekhan S, Baniasadi H, Ramazani A, Ansarizadeh M (2018) Design and fabrication of conductive nanofibrous scaffolds for neural tissue engineering: process modeling via response surface methodology. Biomater Appl. https://doi.org/10.1177/0885328218808917 Song Q, Jiang Z, Li N, Liu P, Liu L, Tang M, Cheng G (2014) Anti-inflammatory effects of three-dimensional graphene foams cultured with microglial cells. Biomaterials 35(25):6930–6940. https://doi.org/10.1016/j.biomaterials.2014.05.002 Stankovich S, Dikin DA, Piner RD, Kohlhaas KA, Kleinhammes A, Jia Y, Ruoff RS (2007) Synthesis of graphene-based nanosheets via chemical reduction of exfoliated graphite oxide. Carbon 45(7):1558–1565. https://doi.org/10.1016/j.carbon.2007.02.034 Subramanian A, Krishnan UM, Sethuraman S (2009) Development of biomaterial scaffold for nerve tissue engineering: biomaterial mediated neural regeneration. J Biomed Sci 16(108):1–11. https://doi.org/10.1186/1423-0127-16-108 Thess A, Lee R, Nikolaev P, Dai H, Petit P, Robert J, Smalley RE (1996) Crystalline ropes of metallic carbon nanotubes. Science 273:483–487. https://doi.org/10.2307/1384782 Thostenson ET, Ren Z, Chou T-W (2001) Advances in the science and technology of carbon nanotubes and their composites: a review. Compos Sci Technol 61:1899–1922. https://doi.org/10.1016/j.matpr.2018.03.038 Treacy MMJ, Ebbesen TW, Gibson JM (1996) Exceptionally high Young’s modulus observed for individual carbon nanotubes. Nature. https://doi.org/10.1038/381678a0 Tupone MG, d’Angelo M, Castelli V, Catanesi M, Benedetti E, Cimini A (2021) A state-of-the-art of functional scaffolds for 3D nervous tissue regeneration. Front Bioeng Biotechnol 9:1–18. https://doi.org/10.3389/fbioe.2021.639765 Urbanczyk M, Layland SL, Schenke-Layland K (2020) The role of extracellular matrix in biomechanics and its impact on bioengineering of cells and 3D tissues. Matrix Biol 85–86:1–14. https://doi.org/10.1016/j.matbio.2019.11.005 Vaia RA, Giannelis EP (1997) Polymer melt intercalation in organically-modified layered silicates: model predictions and experiment. Macromolecules 30(25):8000–8009. https://doi.org/10.1021/ma9603488 Vaia R, Baur J (2008) Adaptive composites. Labour’s Lost Lead 319:420–421. https://doi.org/10.5040/9780755621101.0007 Vicentini N, Gatti T, Salerno M, Hernandez Gomez YS, Bellon M, Gallio S, Menna E (2018) Effect of different functionalized carbon nanostructures as fillers on the physical properties of biocompatible poly(L-lactic acid) composites. Mater Chem Phys 214:265–276. https://doi.org/10.1016/j.matchemphys.2018.04.042 Wang J, Musameh M, Lin Y (2003) Solubilization of carbon nanotubes by nafion toward the preparation of amperometric biosensors. JACS 125:2408–2409 Wang J, Shi Z, Ge Y, Wang Y, Fan J, Yin J (2012a) Solvent exfoliated graphene for reinforcement of PMMA composites prepared by in situ polymerization. Mater Chem Phys 136(1):43–50. https://doi.org/10.1016/j.matchemphys.2012.06.017 Wang P, Ma J, Wang Z, Shi F, Liu Q (2012b) Enhanced separation performance of PVDF/PVP-g-MMT nanocomposite ultrafiltration membrane based on the NVP-grafted polymerization modification of montmorillonite (MMT). Langmuir 28(10):4776–4786. https://doi.org/10.1021/la203494z Wang J, Gao W, Zhang H, Zou M, Chen Y, Zhao Y (2018a) Programmable wettability on photocontrolled graphene film. Sci Adva. https://doi.org/10.1126/sciadv.aat7392 Wang J, Tian L, Chen N, Ramakrishna S, Mo X (2018b) The cellular response of nerve cells on poly-L-lysine coated PLGA-MWCNTs aligned nano fibers under electrical stimulation. Mater Sci Eng, C 91:715–726. https://doi.org/10.1016/j.msec.2018.06.025 Wang J, Zheng W, Chen L, Zhu T, Shen W, Fan C, Mo X (2019a) Enhancement of Schwann cells function using graphene-oxide-modified nanofiber scaffolds for peripheral nerve regeneration. ACS Biomater Sci Eng. https://doi.org/10.1021/acsbiomaterials.8b01564 Wang N, Dang M, Zhang W, Lei Y, Liu Z (2019b) Enhancement of Schwann cells function using graphene-oxide-modified nanofiber scaffolds for peripheral nerve regeneration. ACS Biomater Sci Eng 5(5):2444–2456. https://doi.org/10.1111/sji.12826 Weaver CL, Cui XT (2015) Directed neural stem cell differentiation with a functionalized graphene oxide nanocomposite. Adv Healthc Mater 4(9):1408–1416. https://doi.org/10.1002/adhm.201500056 Wong M, Paramsothy M, Xu XJ, Ren Y, Li S, Liao K (2003) Physical interactions at carbon nanotube-polymer interface. Polymer 44(25):7757–7764. https://doi.org/10.1016/j.polymer.2003.10.011 Wu S, Duan B, Lu A, Wang Y, Ye Q, Zhang L (2017) Biocompatible chitin/carbon nanotubes composite hydrogels as neuronal growth substrates. Carbohyd Polym 174:830–840. https://doi.org/10.1016/j.carbpol.2017.06.101 Xia L, Zhu W, Wang Y, He S, Chai R (2019a) Regulation of neural stem cell proliferation and differentiation by graphene-based biomaterials. Neural Plast 2019:1–12. https://doi.org/10.1155/2019/3608386 Xia Y, Li S, Nie C, Zhang J, Zhou S, Yang H, Haag R (2019b) A multivalent polyanion-dispersed carbon nanotube toward highly bioactive nanostructured fibrous stem cell scaffolds. Appl Mater Today 16:518–528. https://doi.org/10.1016/j.apmt.2019.07.006 Xu Y, Wang Y, Liang J, Huang Y, Ma Y, Wan X, Chen Y (2009) A hybrid material of graphene and poly (3,4-ethyldioxythiophene) with high conductivity, flexibility, and transparency. Nano Res 2(4):343–348. https://doi.org/10.1007/s12274-009-9032-9 Xu M, Zhu J, Wang F, Xiong Y, Wu Y, Wang Q, Liu S (2016) Improved in vitro and in vivo biocompatibility of graphene oxide through surface modification: poly(Acrylic Acid)-functionalization is superior to PEGylation. ACS Nano. https://doi.org/10.1021/acsnano.6b00539 Xu X, Wang J, Wang Y, Zhao L, Li Y, Liu C (2018) Formation of graphene oxide-hybridized nanogels for combinative anticancer therapy. Nanomed Nanotechnol Biol Med 14(7):2387–2395. https://doi.org/10.1016/j.nano.2017.05.007 Yan L, Zhao B, Liu X, Li X, Zeng C, Shi H, Liu Y (2016) Aligned nanofibers from polypyrrole/graphene as electrodes for regeneration of optic nerve via electrical stimulation. ACS Appl Mater Interfaces 8(11):6834–6840. https://doi.org/10.1021/acsami.5b12843 Yang CY, Huang WY, Chen LH, Liang NW, Wang HC, Lu J, Wang TW (2021) Neural tissue engineering: the influence of scaffold surface topography and extracellular matrix microenvironment. J Mater Chem B 9(3):567–584. https://doi.org/10.1039/d0tb01605e Yu AM, Lourie O, Dyer MJ, Moloni K, Kelly TF, Ruoff RS, Ruoff RS (2000) Linked references are available on JSTOR for this article: strength and breaking mechanism of multiwalled carbon nanotubes under tensile load. Science 287(5453):637–640 Yuan X, Zhang X, Sun L, Wei Y, Wei X (2019) Cellular toxicity and immunological effects of carbon-based nanomaterials. Part Fibre Toxicol 16(18):1–27. https://doi.org/10.1186/s12989-019-0299-z Zadpoor AA (2015) Mechanics of biological tissues and biomaterials: current trends. Materials 8(7):4505–4511. https://doi.org/10.3390/ma8074505 Zhang YS, Khademhosseini A (2017) Advances in engineering hydrogels. Science 356(6337):1–10. https://doi.org/10.1126/science.aaf3627 Zhang S, Yang K, Feng L, Liu Z (2011) In vitro and in vivo behaviors of dextran functionalized graphene. Carbon 49(12):4040–4049. https://doi.org/10.1016/j.carbon.2011.05.056 Zhang Q, Wu Z, Li N, Pu Y, Wang B, Zhang T, Tao J (2017) Advanced review of graphene-based nanomaterials in drug delivery systems: Synthesis, modification, toxicity and application. Mater Sci Eng, C 77(1200):1363–1375. https://doi.org/10.1016/j.msec.2017.03.196 Zhao Y, Gong J, Niu C, Wei Z, Shi J, Li G, Wang H (2017) A new electrospun graphene-silk fibroin composite scaffolds for guiding Schwann cells. J Biomater Sci Polym Ed 28(18):2171–2185. https://doi.org/10.1080/09205063.2017.1386835 Zhou K, Motamed S, Thouas GA, Bernard CC, Li D, Parkington HC, Forsythe JS (2016) Graphene functionalized scaffolds reduce the inflammatory response and supports endogenous neuroblast migration when implanted in the Adult Brain. PLoS ONE 11(3):1–15. https://doi.org/10.1371/journal.pone.0151589 Zhu W, O’Brien C, O’Brien JR, Zhang LG (2014) 3D nano/microfabrication techniques and nanobiomaterials for neural tissue regeneration. Nanomedicine 9(6):859–875. https://doi.org/10.2217/nnm.14.36 Zhu W, Harris BT, Zhang LG (2016) Gelatin methacrylamide hydrogel with graphene nanoplatelets for neural cell-laden 3D bioprinting. In: Proceedings of the Annual International Conference of the IEEE Engineering in Medicine and Biology Society, EMBS, 2016-Octob, pp 4185–4188. https://doi.org/10.1109/EMBC.2016.7591649 Zuo KJ, Gordon T, Chan KM, Borschel GH (2020) Electrical stimulation to enhance peripheral nerve regeneration: Update in molecular investigations and clinical translation. Exp Neurol 332:113397. https://doi.org/10.1016/j.expneurol.2020.113397